The possible role of oncogenes in the development of human hepatocellular carcinoma (HCC) has not been well defined. We have examined several cell lines from human HCC, as well as a control (non-HCC) cell line (WI-38) for levels of expression of oncogenes. The expression of thirteen oncogenes (c-myc, H-ras, K-ras, N-ras, raf, Mb, abl, N-myc, erb-A, erb-B, fos, src, and mos) and two tumor suppressor genes (Rb and p53) were studied by northern blot hybridization in three human HCC/HB cell lines (PLC/PRF/5, Hep3B, and Hep G2) and in a human embryonic lung fibroblast cell line (WI-38) to look for differences that might be associated with the presence (PLC/PRF/5 and Hep3B) or absence (Hep G2) of integrated hepatitis B virus (HBV) DNA. Most of the oncogenes were expressed at a higher level (based on band intensity) in HCC/HB cell lines than in WI-38 cell lines (exceptions: K-ras, fos, and Rb were expressed at the same level in all four cell lines; p53 was not detectable in Hep3B). Certain oncogenes (c-myc, H-ras, raf, src) were expressed at different levels among the three HCC/HB cell lines, unrelated to the presence or absence of integrated HBV-DNA. Additional studies were conducted using additional human HCC cell lines: 2.2.15 (which is derived from Hep G2 transfected with HBV) and the three Japanese lines: HLE, HLF, and HuH7. The data for these lines are still being analyzed.